Evidence for Kekule s model to be wrong: STANDARD ANSWERS AND DEFINITIONS All C-C bond lengths are the same length, between C-C and C=C. Only reacts with Br2 with a halogen carrier Benzene is lower in energy than Kekule s structure suggests its should be. Discuss the structure and bonding in benzene / (comparing to kekule - structure): Label p orbitals and state that they overlap Label delocalised orbitals State the bond lengths are the same That it is a planar molecule Discuss the relative low reactivity of benzene / (problems with Kekule reactivity): Draw the enthalpy diagram This shows that benzene is not 3 c=c as it is lower in energy This means it is more stable Therefore is less reactive Discuss the reactivity of benzene compared to alkenes Between the C-C: 2e from a bond and 2e from the localised bond = 4e Higher electron density Polarises electrophiles more. Alkenes do not need halogen carrier. Electrophilic addition reactions Between the C-C: 2e from bond and 1e pre C-C from delocalised bond = 3e Lower electron density Polarises electrophiles less. Benzene needs a halogen carrier. Electrophilic substitution reactions Discuss the reactivity of phenol compared to benzene
Lone pair electrons on the O Delocalise with the electrons in the benzene ring Makes it more electron rich Ring becomes activated Polarises electrophiles more. Phenols do not need halogen carrier. Are multiply substituted. Between the C-C: 2e from bond and 1e from C-C from delocalised bond = 3e Lower electron density Polarises electrophiles less. Benzene needs a halogen carrier. Only monosubstituted Summary: Benzene VS. Cyclohexene Cyclohexene Electrophillic Addition Electrons are localised Between C-C 2e from bond and 2e from localised bond = 4e Higher electron density, polarises electrophiles more Don t need a halogen carrier Benzene Electrophillic Substitution Electrons are delocalised Between C-C 2e from bond and 1 e from the C-C from delocalised bond = 3e Lower electron density, polarises electrons less Need a halogen carrier Benzene VS. Phenol Phenol- Multiple Substitution Lone pair of electrons on O Delocalise with the electrons in the Benzene ring Makes more electron rich Ring becomes activated, polarises electrophiles more Phenols do not need a halogen carrier Benzene- Mono-substitution Electrophillic Substitution Electrons are delocalised Between C-C 2e from bond and 1 e from pre C-C from delocalised bond = 3e Lower electron density, polarises electrons less Need a halogen carrier
Nitration of benzene: Conc H 2 SO 4 C 6 H 6 + HNO 3 C 6 H 5 NO 2 + H 2 O Reflux 50 o C Generation of the electrophile: Conc conc HNO 3 + H 2 SO 4 + NO 2 + - HSO 4 Nitryl ion is electrophile + H 2 O Regeneration of the catalyst: H + + HSO 4 - H 2 SO 4 Halogenation of benzene: FeBr 3 C 6 H 6 + Br 2 C 6 H 5 Br + HBr Generation of the electrophile: FeBr 3 + Br 2 Br + + FeBr 4 - Bromonium ion is electrophile Regeneration of the catalyst: H + + FeBr 4 - FeBr 3 + HBr
Carbonyl Test Test for Carbonyl Group 2,4,DNPH (Brady s Reagent) If present, orange precipitate formed FILTER, RECRYSTALISE, FILTER, MELTING POINT DETERMINATIO0N / COMPARE TO KNOW DATA Test to distinguish between Aldehyde and Ketone Warm with Tollens Reagent (silver nitrate dissolved in ammonia) If aldehyde present, silver mirror forms as the aldehyde is oxidised If ketone present no change as ketone cannot be oxidised Reduction of Aldehydes / ketonesmechanism of reducing an Aldehyde NaBH 4 : Source of hydride ions, H -
Azo Dyes 1) Make Nitrous Acid NaNO2 + HCl NaCl + HNO2 (below 10oC) 2) Make Diazonium Salt Below 10 o C because N 2 is unstable decomposes releasing nitrogen gas Benzenediazonium salts are stabilized as the benzene ring allows the electrons from the diazonium functional group to be delocalised over the benzene ring 3) Coupling The Azo dye is now stable as there is extensive delocalisation over both arenas via the azo group, -N=N- This also gives rise to the colours Amines A weak base because of lone pair of electrons on N accept protons proton acceptors lone pair electrons are donated forming a dative covalent bond Inductive Effect Alkyl groups- positive inductive effect stronger base The alkyl group gives a small push of electrons towards LP on the N This makes it form a dative covalent bond more readily Ammonia - no inductive effect as nothing attached to functional group Benzene Ring Negative inductive effect Benzene ring has small pull of electrons away from Nitrogen atom The LP electrons are delocalised into the benzene ring Makes them less readily available to form a dative covalent bond Weaker base
Fatty acid - shorthand: Fatty acids can be written in shorthand: Number of carbon atoms Number of double bonds Position of double bonds 18 : 1 (9) Fatty Acid Risk Reason Packing State Cause Saturated Heart disease Raises blood cholesterol Close Solid Blocks arteries Coronary heart Trans disease Unsaturated Cis No Health risk Raises blood cholesterol Close Cannot pack close together Solid Blocks arteries Liquid No effect Trans fats cholesterol: High Density Lipoproteins Carry cholesterol out of the blood and out of the body Good Low Density Lipoproteins Carry about 65% of cholesterol around the body and deposit lipids onto artery walls This restricts blood flow Bad Making Biodiesel - Transesterification: The waste oil is filtered then reacted with methanol and sodium hydroxide (catalyst) to form biodiesel. This also increases the atom economy of fats. Preparation of Alphatic Amines Warm halogenoalkens with excess ammonia CH3CH2Cl + NH3 CH3CH2NH2 + HCl NH3 + HCl NH4Cl
Preparation of Primary/Secondary aliphatic amines CH3CH2NH2 + CH3CH2Cl (CH3CH2)2NH (CH3CH2)2NH + CH3CH2Cl (CH3CH2)3N Isoelectric Point Usually PH6 as COOH is slightly more acidic that NH2 is basic Depends on side groups, hence the different points Acid Hydrolysis Heat under reflux with 6mHCl for 24 hours + Always gives COOH and NH 3 Alkali Hydrolysis Solution of NaOH, reflux Always gives COO - Na + and NH 2 Hydrolysis of Polyesters/Polyamides Hot aq Acid/ aq Alkali As above for acid / alkali hydrolysis products Photodegradable polymers Blended with light sensitive catalysts so become weak, brittle when exposed to light Can also have C=O which absorb UV light and break Photodegradable plastics break to form shorter waxy hydrocarbon molecules before bacteria breaks them further into CO2 and H2O Chromatography Stationary phase is in a fixed place (paper in paper chromatography) molecules interact with stationary phase slowing down their movement ADSORPTION Mobile phase moved in a definite direction (water rises up in paper chromatography) molecules interact with mobile phase speeding up their movement SOLUBILITY Thin Layer Chromatography TLC Is used to check purity / separate amino acids/ monitor the extent of a reaction. Solid stationary phase- Silica Gel Liquid mobile phase- Solvent Producing the chromatogram in TLC: Dissolve sample. Draw a pencil line and spot sample using a capillary tube, allow to dry. Place plate in a tank of solvent - solvent must be below line, seal the tank. Separation is by adsorption - allow solvent to almost reach the top, draw a line here - solvent front.
Each separated component is a spot, if colourless use ninhydrin and a UV lamp Limitations of TLC Similar compounds often have too similar R f values. Unknown compounds have no R f value for comparison. It is hard to find a solvent that will have the correct amount of solubility - Goldilocks!! R f = Distance moved by component Distance moved by solvent front Gas Chromatography - GC Is used to separate volatile compounds (gases) in a mixture with low boiling points The stationary phase: Depends what is separated whether you use a liquid or solid lining of the chromatography column e.g liquid long chain alkane (high boiling point) e.g solid silicone polymer The mobile phase: Inert carrier gas e.g helium or nitrogen. Separation Different components slowed by different amounts- separation retention times Each component leaves the column at a different time and is detected as it leaves the column. Each peak represents a component Area under each peak is proportional to the abundance of each component Limitations of gas chromatography: Similar retention times + peak shapes most compounds cannot be positively identified. Not all substances can be separated. Unknown compounds have no reference retention times. Due to the limitations, gas chromatography is usually used in conjunction with spectroscopy. Uses for GC-MS 1) Forensics - scenes of crime 2) Environmental analysis - air pollutants, waste water, pesticides in food. 3) Airport security - explosives in luggage / airport security 4) Space probes - planetary atmospheres
Chiral Compound Optical isomers are one type of Stereo isomers (cis / trans is the other). They are non-superimposable Chiral carbon has 4 different groups attached Always draw in 3D Properties of optical isomers: They rotate plane polarised light. One isomer rotates it in one direction and the other in the opposite direction Problems with Chiral drugs One optical isomer may have serious side effects Expensive/ difficult to separate isomers One optical isomer may have serious side effects Reduces the effectiveness Dose size Overcoming Chiral drug synthesis problems Use and enzyme catalyst Chiral Synthesis Chiral Catalyst Chiral Pool Synthesis 1) Using enzymes as biological catalysts: Nature is steroespecific, if this can be used only one isomer will be produced. If a biocatalyst is used it will only catalyse the production of one isomer. 2) Chiral pool synthesis: This starts the synthesis pathway with a stereospecific enantiomer All of the following synthesis steps should lead to a pure optical isomeric drug 3) Use of transition metal complexes: Some act as catalysts that will produce only one optical isomer Cause of Stereo Isomerism a) Optical isomerism C with 4 different groups attatched Mirror images of each other b) Cis trans isomerism C=C has restricted rotation Both C in C=C attached to two different groups NMR: Interpretation: always gives you 2 pieces of information 1) splitting pattern number of adjacent H s 2) Chemical shift adjacent functional groups If the numbers of H s are given above the peak, make sure you use these too
D2O D replaces H in OH and NH protons Peak for OH / NH protons disappears This is due to D having 2 nucleons no signal TMS Reference Signal at 0 DEFINITIONS Retention time- Is the time taken for a component to pass from inlet to detector. Alpha Amino Acid-NH2 and COOH joined at the same C Stereoisomers-Same structural formula different spatial arrangement of atoms Amphoteric- Amino acids will react with both acids due to NH2 and alkalis due to COOH Optical isomers- Mirror images cannot be superimposed upon each other Achiral compounds- do not have 4 different groups around a carbon atom Chiral compounds- have 4 different groups around a carbon atom Enantiomers- the two different optical isomers Racemic mixture - An equal mixture of the 2 isomers will not rotate plane polarised light as each isomer cancels the other out. Stereospecific - Optical activity is important in biological systems as only one of the isomers will interact with enzymes. Delocalised electrons are shared between more than 2 atoms Addition reaction where a reactant is added to an unsaturated molecule Substitution reaction where an atom or group of atoms is replaced with a different atom/group of atoms Electrophile is an atom/group of atoms that is attracted to an electron rich centre where it accepts a pair of electrons to form a dative covalent bond Substitution is where one group is replaced by another group Curly arrow used in mechanisms to show the movement of an electron pair / forming, breaking bonds.